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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 91 records · Page 5Linked to original sources

Effect of pumping with injection of sodium hyaluronate and the other factors related to outcome in patients with non-reducing disk displacement of the temporomandibular joint.

We retrospectively examined the effect of pumping with injection of sodium hyaluronate into the temporomandibular joint (TMJ) and the other factors influencing outcome in patients with non-reducing disk displacement of the TMJ. Fifty-nine patients underwent pumping with injection of sodium hyaluronate into the TMJ. As control, 62 patients were observed without any treatment. Both groups were observed for 12 months. The relation between outcome and the following clinical characteristics was also studied: sex, age, range of motion for maximal mouth opening, TMJ pain, TMJ noise, tenderness of masticatory muscles, locking duration, intercuspal occlusions, angle of posterior slope of articular eminence and degenerative bony changes of the condyle. Logistic regression analysis revealed that pumping with injection of sodium hyaluronate was related to a good outcome. Clinical characteristics of presentation significantly related to a good outcome were a large maximal mouth opening, a short locking duration, and a steep posterior slope of articular eminence. We conclude that pumping with injection of sodium hyaluronate into the TMJ is an effective treatment method for non-reducing disk displacement of the TMJ and that some clinical characteristics also influence outcome.

Adjuvants, Immunologic↗

Prognostic factors of patients with yolk sac tumors of the ovary.

OBJECTIVE: Our purpose was to evaluate the prognostic factors in yolk sac tumors of the ovary. STUDY DESIGN: We performed a retrospective review of 47 patients with yolk sac tumors of the ovary from 1979 to 1997. RESULTS: Twenty-two patients had pure yolk sac tumors and 25 had germ cell tumors with yolk sac tissue as a component of the disease. The 5-year survival rate in stages I, II, III, and IV was 95%, 75%, 30%, and 25%, respectively. Patients with stage I disease had a more favorable prognosis than those with stage III and IV disease (P <.001). All patients who did not respond to chemotherapy died of this disease within 36 months of the first treatment. Chemotherapy regimens that included cisplatin gave better results than those without cisplatin (P <.05). The difference in prognosis was significant in cases in which the size of residual tumor was <2 cm in diameter (P <.01) and in cases in which ascites was either absent or <100 mL in volume (P <.05). Coexistence of other components of ovarian germ cell tumors in histologic specimens, preoperative serum alpha-fetoprotein level, fertility-sparing surgery, dissection of intrapelvic nodes, and p53 status had no significant correlation with the prognosis in this study. CONCLUSIONS: Staging and tumor-reductive surgery strongly affected the prognosis of this disease. Tumor-reductive surgery is advisable when ascites is minimal. Cisplatin-based chemotherapy after surgery was superior to chemotherapy without cisplatin; however, p53 status seemed to have no impact on chemosensitivity in yolk sac tumors of the ovary.

Antineoplastic Combined Chemotherapy Protocols↗

Two distinct mechanisms are involved in stent thrombosis under flow conditions.

The mechanism of stent thrombosis was evaluated by a flow chamber model. A Palmaz-Schatz stent was placed on glass surfaces coated with type I collagen in a parallel-plate flow chamber. Platelets were rendered fluorescent with mepacrine and whole blood was perfused through the chamber. Platelet thrombi formed around the implanted stents were continuously recorded by epi-fluorescent video-microscopy. Platelet thrombi appeared on the collagen surface within a few minutes in the absence of function blocking monoclonal antibodies. Antibody blocking vWF interaction with GP Ib alpha completely inhibited the platelet thrombi around the stent, but had no effect on platelet thrombus formation in the space between the stents and collagen, while both were inhibited by anti-GP IIb/IIIa. Our results suggest that two distinct mechanisms, one mediated by vWF interaction with GP Ib alpha occurring at high shear rates, and the other mediated exclusively by GP IIb/IIIa occurring at low shear rates, are involved in the process of platelet thrombus formation in the presence of stents.

Animals↗

Effects of ticlopidine on von Willebrand factor-mediated shear-induced platelet activation and aggregation.

Ticlopidine, recently classified as a P2Y(12) ADP receptor blockade, is known to be an effective antiplatelet agent preventing arterial thrombosis, e.g., myocardial infarction or cerebral infarction, but the mechanism of the in vivo antithrombotic effects of ticlopidine is not fully understood. Blood was drawn from seven normal volunteers before and 7 days after consecutive intake of ticlopidine, and 1 day after oral intake of aspirin after 7 days of ticlopidine wash-out period. Effects of drug intake on shear-induced von Willebrand factor (vWF) binding to platelets, platelet activation evidenced by P-selectin surface expression and translocation of GP Ibalpha, and vWF-mediated platelet aggregation, were investigated by using an optically modified cone-plate viscometer and quantitative flow cytometry. The maximum extent of platelet aggregation occurring under a high shear rate of 10800 s(-1), presumably mediated by vWF, was not significantly influenced by either ticlopidine or aspirin. However, significant dissociation of once aggregated platelets occurred in samples obtained after ticlopidine intake (25.4 +/- 9.3%, P = 0.00030) and less significantly after aspirin intake (15.9 +/- 5.7%, P = 0.0013), while only insignificant and modest dissociation occurred in controls (6.3 +/- 4.4%, n.s.). Binding experiments also revealed that the shear-induced vWF binding to platelets was significantly inhibited by ticlopidine, and less significantly by aspirin, although other indicators of platelet activation, such as shear-induced P-selectin expression and GP Ibalpha translocation were not influenced by either ticlopidine or aspirin. We demonstrate here that platelet aggregation mediated by von Willebrand factor (vWF) under a high shear rate of 10800 s(-1) cannot be stabilized and that dissociation occurs readily when ADP receptor stimulation is blocked by continuous intake of ticlopidine, indicating that these effects on platelet thrombus formation may contribute to the in vivo antithrombotic effects of ticlopidine.

Adult↗

Messenger ribonucleic acid for the mouse decidual prolactin is present and induced during in vitro decidualization of endometrial stromal cells.

Although decidualization of endometrial stromal cells is crucial for blastocyst implantation and maintenance of pregnancy, its complex mechanism still remains largely unknown. To explore the mechanisms of decidualization, we have established an in vitro decidualization model in mice. Through extraction of mRNA from endometrial stromal cells for subsequent reverse transcriptase polymerase chain reaction analysis, we found that two ovarian hormones, 17 beta-estradiol and progesterone, induced morphological changes and expression of mRNA for prolactin (PRL) and the decidual/trophoblastic PRL-related protein (d/tPRP) in cultured mouse endometrial stromal cells. The expression of mRNA for the decidual PRL was also detected in the mouse decidua in vitro. In conclusion, mouse mRNA for decidual PRL is present and induced by estradiol and progesterone through in vitro decidualization of endometrial stromal cells.

Animals↗

Effects of pranlukast, a leukotriene receptor antagonist, on airway inflammation in mild asthmatics.

To determine the anti-inflammatory actions of pranlukast, a cysteinyl leuklotriene receptor antagonist, we measured exhaled nitric oxide (NO) concentrations and eosinophil ratio in induced sputum of three groups of mild asthmatics (n = 30): treated with bronchodilators alone, with bronchodilators and inhaled steroid (beclomethasone dipropionate; 400 microg/day), and bronchodilators and pranlukast (450 mg/day). Pranlukast (450 mg/day) reduced the eosinophil ratio in the induced sputum significantly (p < 0.01) without a major effect on the concentration of exhaled NO. Pranlukast also increased values of peak expiratory flow significantly (p < 0.05). Pranlukast may be useful for mild asthmatics, in part through its ability to suppress eosinophilic airway infiltration.

Adult↗

Early-generated preplate neurons in the developing telencephalon: inward migration into the developing striatum.

Specialized subsets of early-generated neurons provide the cellular cues that are necessary for the establishment of characteristic cell and fiber interactions in each brain region. During the development of the mammalian cerebral cortex, the early-generated cells line up in the most superficial part of the telencephalic pallium forming the preplate. It has been generally thought that the preplate derivatives are exclusively located in the cortical region and govern the early histogenetic phase of cortical development. However, we here disclose an unexpected evidence that a subset of early-generated neurons of the piriform preplate migrate inward into and disperse within the subcortical structure striatum during the embryonic stage. Their migratory route is unique and its direction is opposite to the ordinary migration of neuronal precursors directed outward from the periventricular germinal zone. After immigrating into the developing striatum, these early-generated cells are closely associated with the intrastriatal fascicules of axons. The majority of these cells are eliminated by apoptotic cell death during the early postnatal stage. Based on these findings, we propose a new concept: the preplate neurons may not only direct cortical histogenesis but also change their location to play a role in the development of subcortical structures.

Animals↗

A resin veneer for enamel protection during orthodontic treatment.

The aims of this study were to test the tensile bond strength of a recently developed veneer. Sound premolar teeth (120) extracted for orthodontic purposes were divided into two experimental and two control groups. In one experimental group (V1) 4-META/MMA-TBB resin (4META) was used on the surface veneer prepared with micro particle filled resin (MFR) as an adhesive for bracketing and in the second group (V2) 4META was applied on the surface veneer with the trial resin. For the controls, in group R 4META was used on the enamel surface without veneer and in group G light-cured glass ionomer cement was applied. The 30 samples in each group were divided into three groups of 10 samples and thermal cycled (TC) at 3000, 10,000 or left uncycled. Tensile testing was carried out using an Instron machine. After tensile testing the bond failures in the experimental groups were recorded using a stereomicroscope. Statistical analysis was performed using ANOVA. In group V2 the resin veneer was able to maintain sufficient bond force to enamel during clinical use. The bond strength of group V1 was significantly higher than that of groups R (P < 0.05) and G (P < 0.01) at TC 0, but for both TC 3000 and 10,000, the bond strength of group V1 was lower than groups R and G, respectively. There were significant differences between groups V1 and R (P < 0.01) for TC 3000, and between groups V1 and R and G (P < 0.01) at TC 10,000. The bond strength of group V2 was almost equal to that of group R at TC 0. At TC 3000, group V2 showed significantly lower bond strength than group R (P < 0.05), but no significant difference was found compared with group G. At TC 10,000, there were no significant differences between groups V2, R or G. When comparing groups V1 and V2, the bond strength of group V1 was significantly higher than that of group V2 (P < 0.01) at TC 0, but the bond strength of group V1 was significantly lower than that of group V2 for both TC 3000 (P < 0.05) and TC 10,000 (P < 0.01). Comparison between groups R and G, showed that the bond strength of group R was significantly higher than that of group G for both TC 0 (P < 0.01) and TC 3000 (P < 0.01), but no significant difference was found for TC 10,000. In group V2, nine samples showed adhesive failure between the veneer surface and bracket adhesive before thermal cycling. There were significant differences between the MFR and both trial resin and glass ionomer cement (P < 0.01) when examining thermal expansion. No significant difference was found between the trial resin and glass ionomer cement. It is suggested that application of a resin veneer prior to bracket bonding is suitable for clinical application to protect the teeth and to prevent decalcification and caries.

Acrylic Resins↗

Doxorubicin-induced DNA intercalation and scavenging by nuclear glutathione S-transferase pi.

Glutathione S-transferase (GST) functions in xenobiotic biotransformation and drug metabolism. Increased expression of GSTpi, an isozyme of GST, has been found in cancer cells resistant to doxorubicin hydrochloride (DOX) or cis-diamminedichloroplatinum (II) (CDDP), and this increase was believed to be correlated with drug resistance of cancer cells. GST is mainly expressed in the cytoplasm; GSTpi in the nucleus has been reported in cancer cells, but the meaning of this result is not known. Here, we studied changes in the amount of nuclear GSTpi after exposure of cancer cells to anticancer drugs, and role of the nuclear GSTpi in drug resistance. We found nuclear GSTpi in cancer cells resistant to DOX, and the amount of nuclear GSTpi was enhanced by treatment of the cancer cells with DOX or CDDP. We also found that a mushroom lectin, an inhibitor of nuclear transport, inhibited the nuclear transfer of GSTpi, suggesting the existence of a specific transport system for the nuclear transfer of GSTpi. Nuclear GSTpi protected DNA against damage by anticancer drugs. These results suggest a possible role of GSTpi in the acquisition of resistance to anticancer drugs by cancer cells.

Antineoplastic Agents↗

Experimental stroke in the female diabetic, db/db, mouse.

Diabetic hyperglycemia increases brain damage after cerebral ischemia in animals and humans, although the underlying mechanisms remain unclear. Gender-linked differences in ischemic tolerance have been described but have not been studied in the context of diabetes. In the current study, we used a model of unilateral common carotid artery ligation, combined with systemic hypoxia, to study the effects of diabetes and gender on hypoxic-ischemic (HI) brain damage in the genetic model of Type II diabetes, the db/db, mouse. Male and female, control and db/db, mice were subjected to right common carotid artery ligation followed by varying periods of hypoxia (8% oxygen/92% nitrogen) to assess mortality, infarct volume, and tissue damage by light microscopic techniques. End-ischemic regional cerebral blood flow (CBF) was determined using [14C] iodoantipyrine autoradiography. Glycolytic and high energy phosphate compounds were measured in blood and brain by enzymatic and fluorometric techniques. Gender and diabetes had significant effects on mortality from HI and extent of brain damage in the survivors. Female mice were more resistant than their male counterparts, such that the severity (mortality and infarction size) in the male diabetics > female diabetics - male controls > female controls. Endischemic CBF and depletion of cerebral high energy reserves were comparable among all groups. Surprisingly, female diabetic mice were more hyperglycemic and demonstrated a greater prolonged lactacidosis than the males; however, they were more resistant to damage. The results suggest a unique pathophysiology of hypoxia-ischemia in the female diabetic brain.

Animals↗

Implications of protein degradation in aging.

Aging is characterized by accumulation of potentially harmful altered proteins that could lead to gradual deterioration of cellular functions and eventually result in increased probability of death. Metabolic turnover of proteins thus plays an essential role in maintaining the life of an organism. In this article we summarize our current knowledge on age-related changes in protein turnover with special reference to degradation. Increase in half-life of proteins with advancing age is well documented. Qualitative rather than quantitative changes of proteasomes appear to be responsible for this change. Dietary restriction and moderate long-term exercise seem to restore higher proteasome activity and turnover rate of proteins in aged animals.

Aging↗

Resistance to multiple agent chemotherapy including cisplatin after chronic low-dose oral etoposide administration in gestational choriocarcinoma.

Most patients with gestational trophoblastic disease in whom single-agent or even combination chemotherapy has failed can be cured with salvage chemotherapy including etoposide or platinum-based regimens. Here we report a rare case of uterine choriocarcinoma following a molar evacuation that seemed to develop during chronic low-dose oral administration of etoposide for approximately 16 months. Although the patient was expected to have a good chance of cure using combination chemotherapy, the lesion was resistant to multiple-agent chemotherapy including cisplatin.

Administration, Oral↗

Hyperthermic enhancement of the apoptotic and antiproliferative activities of paclitaxel.

The antineoplastic agent paclitaxel (PTX), a microtubule-stabilizing agent, is known to arrest cell cycle progression and induce apoptosis. Mild hyperthermia (HT) also disrupts the microtubule system and triggers apoptosis. We therefore investigated whether concurrent exposure of murine breast cancer cells to 10 micromol/l PTX and 43 degrees C HT will promote improved anticancer effects. To do this, we exposed FM3A murine cancer cells to: (1) 10 micromol/l PTX for 1 h at 37 degrees C followed by exposure at 43 degrees C HT for 1 h; (2) 10 micromol/l PTX at 37 degrees C for 2 h; (3) 37 degrees C for 1 h followed by 43 degrees C HT for 1 h, and (4) untreated cells at 37 degrees C for 2 h which served as the control. Treatment No. 1 resulted in an enhanced cell cycle arrest, apoptosis and cytotoxicity. Exposure to 43 degrees C HT alone or 10 micromol/l PTX alone induced lesser apoptosis and cytotoxicity than the two treatments concurrently applied. The apoptotic cell death occurred in a time-dependent manner as follows: (1) concurrently applied 43 degrees C HT and 10 micromol/l PTX (5.6 +/- 0.5, 16.5 +/- 2 and 27.6 +/- 1%); (2) 43 degrees C HT alone (4.3 +/- 1, 6.6 +/- 0.3 and 12.7 +/- 1%) and (3) 10 micromol/l PTX alone (4.4 +/- 0.3, 8.6 +/- 1 and 12.8 +/- 1%) at 1, 6 and 24 h postexposure respectively compared to control of 2.0%. These data indicate that while both HT and PTX can individually induce apoptosis and antiproliferation in FM3A cancer cells, they may offer synergistic benefits when used concurrently.

Animals↗

Neuroprotective effect of sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) is linked to reduced neuronal nitric oxide production.

BACKGROUND AND PURPOSE: The potent final sigma(1)-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) provides neuroprotection in experimental stroke. We tested the hypothesis that PPBP attenuates striatal tissue damage after middle cerebral artery occlusion (MCAO) by a mechanism involving reduction of ischemia-evoked nitric oxide (NO) production. Furthermore, we determined whether the agent fails to protect ischemic brain when neuronal nitric oxide synthase (nNOS) is genetically deleted or pharmacologically inhibited (selective nNOS inhibitor, 7-nitroindazole [7-NI]). METHODS: Halothane-anesthetized adult male Wistar rats were subjected to 2 hours of MCAO by the intraluminal filament occlusion technique. All physiological variables were controlled during the ischemic insult. In vivo striatal NO production was estimated via microdialysis by quantification of local, labeled citrulline recovery after labeled arginine infusion. In a second series of experiments, nNOS null mutants (nNOSKOs) and the genetically matched wild-type (WT) strain were treated with 90 minutes of MCAO. Brains were harvested at 22 hours of reperfusion for measurement of infarction volume by triphenyltetrazolium chloride histology. RESULTS: PPBP attenuated infarction volume at 22 hours of reperfusion in cerebral cortex and striatum and markedly attenuated NO production in ischemic and nonischemic striatum during occlusion and early reperfusion. Treatment with 7-NI mimicked the effects of PPBP. In WT mice, infarction volume was robustly decreased by both PPBP and 7-NI, but the efficacy of PPBP was not altered by pharmacological nNOS inhibition in combined therapy. In contrast, PPBP did not decrease infarction volume in nNOSKO mice. CONCLUSIONS: These data suggest that the mechanism of neuroprotection of PPBP in vivo is through attenuation of nNOS activity and ischemia-evoked NO production. Neuroprotective effects of PPBP are lost when nNOS is not present or is inhibited; therefore, PPBP likely acts upstream from NO generation and its subsequent neurotoxicity.

Animals↗

Platelet aggregability under shear is enhanced in patients with unstable angina pectoris who developed acute myocardial infarction.

The study investigated whether patients hospitalized for unstable angina pectoris (UAP), who subsequently develop complete coronary thrombosis (acute transmural myocardial infarction (AMI)) despite medical treatment, exhibit platelet hyperaggregability in an assay system that does not employ agonist stimulation. The study comprised 89 patients with UAP (Braunwald type B). Unfractionated heparin and nitrate were administered to all patients via continuous intravenous drip together with aspirin taken orally. Citrated platelet-rich plasma (230-250x 10(3)/microl) was obtained on admission and again, in some patients, following the AMI. Platelet aggregability was measured in an optically modified cone-plate viscometer that enables the detection of platelet aggregation without agonist stimulation. A continuous shear rate of 1,200/s was employed. Of the 89 patients, 85 were finally stabilized, while 4 developed an AMI accompanied by persistent ST-segment elevation with increased levels of plasma creatine kinase within 3 h after starting the treatment. The extent of platelet aggregation on admission was significantly greater in these 4 patients compared with the 85 who were stabilized (87.8+/-6.8%, n=4 vs 26.8+/-9.1%, n=85; mean+/-SD). These data suggest that platelet hyperaggregability mediated mainly by fibrinogen binding to the activated glycoprotein IIb/IIIa complex occurs before a complete thrombotic occlusion and this evaluation may provide important information before the onset of myocardial infarction.

Aged↗

The circadian blood pressure rhythm in non-diabetic hemodialysis patients.

This study investigates the circadian blood pressure variation of non-diabetic chronic hemodialysis (HD) patients on both HD and non-HD days as well as the factors affecting diurnal BP variation. Forty-nine HD patients aged 61.8 +/- 12.9 years who were on daytime HD for 97 +/- 68 months were studied. No significant difference was found in every daytime and nighttime BP between the first (HD) and the second (non-HD) day. However, the ratio nighttime/daytime BP was significantly higher on the second day. Each BP diurnal variability pattern was classified as either Dipper (D: the ratio nighttime/daytime mean BP 0.8-0.9), non-dipper (0.9 < ND < 1.0), or inverted dipper (ID > 1.0). More than 75% of the cases were classified as ND (26 cases) or ID (11 cases). The ultrafiltration rate in D was significantly less than that in ND and ID. The difference of plasma renin activity between pre- and post-HD (dRen) was significantly higher in ID than in D and ND. The amount of dialysis (Kt/V) was found to be significantly correlated with nighttime BP fall. Ultrafiltration, dRen and Kt/V were independent factors for the abnormal BP diurnal variability. In conclusion, the decreased nocturnal BP fall seen in non-diabetic HD patients is associated with increased extracellular fluid even in the patients without overt overhydration, whereas relatively insufficient amount of dialysis (low Kt/V) may be another possible cause. The increased dRen observed only in ID patients may reflect occult cardiovascular damage or functional disturbances in aortic and carotid baroreflexes caused by arterial structural changes.

Adult↗

Association of gene polymorphism of polymeric immunoglobulin receptor and IgA nephropathy.

OBJECTIVE: In order to explore the possibility that genetic predisposition to dysfunction of mucosal immunity and the IgA processing pathway plays a role in the pathogenesis of mesangial IgA1 deposition in IgAN, we examined the possible association of the gene polymorphism of pIgR in the patients with and without IgAN. SUBJECTS AND METHODS: Genomic DNA of peripheral blood cells was isolated from 372 individuals including 172 histologically confirmed IgAN patients. Segments of the pIgR gene were PCR amplified and restriction fragment length polymorphism was determined as A1 and A2 with and without Pvu II site, respectively. RESULTS: The pIgR genotype distribution was significantly different between the patients with IgAN and those without IgAN. Allele frequency of A2 was higher in IgAN than in other renal diseases (A1 and A2; 0.516 and 0.484 in IgAN, 0.641 and 0.359 in others, chi2 = 9.84, P = 0.0017, Odds ratio = 1.71). Moreover, the subjects with A2A2 genotype were associated with a relatively low level of serum IgA only in the patients with IgAN but not in other renal diseases. The difference of allele frequencies was more remarkable in the patients with a serum IgA level of less than 300 mg/dl (A1 and A2; 0.439 and 0.561 in IgAN, 0.702 and 0.298 in others, chi2 = 12.44, P = 0.0004, Odds ratio = 3.01). CONCLUSION: This is the first demonstration of the pIgR gene polymorphisms in IgAN which are associated with its clinical phenotype. Gene polymorphisms of pIgR may be candidate genetic markers of susceptibility to IgAN.

Alanine↗

The invasive features of glial and non-central nervous system tumor cells are different on organotypic brain slices from newborn rats.

On radiograms, glial tumors are usually seen to invade in a finger-like fashion, while non-central nervous system (CNS) tumors expand in a mass-like fashion. We prepared organotypic brain slice cultures from newborn rats to investigate the invasive behavior of human brain tumors using glial tumor cell lines (U-87MG, U-373MG, U-251MG, and SF-126) and of non-CNS tumors using cell lines; HT-1080 (human malignant fibrosarcoma), RFRF (human lung carcinoma), MIA-PICA (human pancreatic carcinoma), and Colo38 (human malignant melanoma). We selected an area that was centered at a junction between deep cortical layers and the striatum, punched a hole measuring 0.5-0.7 mm in diameter in this area, implanted different rhodamine-labeled tumor cells at that site, and observed their invasive behavior under an inverted fluorescent microscope. Over the course of several days, all glioma cells invaded in a finger-like fashion; U-373 MG cells invaded farthest. Non-CNS tumors expanded in mass-like fashion into adjacent areas. Using the slice cultures, we also investigated the regulatory effect on tumor invasion of forced expression of glial fibrillary acidic protein (GFAP) after gene transfection. The forced expression of GFAP rendered U-87MG and HT-1080 cells less invasive. Our results show that organotypic brain slice cultures are an excellent medium for studying the invasive features of glial and non-CNS tumors.

Animals↗